Review
Chemistry, Analytical
Di Yu, Lina Zhou, Xinyu Liu, Guowang Xu
Summary: The introduction of stable isotope labeling (SIL) technology has become a routine tool for functional metabolomics studies and allows for a deeper understanding of dynamic metabolic regulation in organisms. Mass spectrometry (MS) techniques have shown great vitality in this field by utilizing the different mass spectrometric characteristics between endogenous metabolites and their isotope-labeling forms. Recent advances in MS-based stable isotope-resolved metabolomics (SIRM) methods have expanded the breadth and depth of SIRM research by improving sample pretreatment, MS analysis, and data analysis. This review describes the recent progress of SIRM methods, summarizes their applications in metabolite identification, accurate quantification, and metabolic flux analysis, and discusses current limitations and challenges.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Applied
Junfu Ji, Xinyu Liu, Xiaosong Hu, Fang Chen, Christoph Bueschl, Rainer Schuhmacher, Andrew L. Waterhouse, Lingjun Ma
Summary: This study successfully identified quinone reaction products in wine using a stable-isotope labelling approach combined with high-resolution mass spectrometry. Different nucleophiles were found to react in white wines and red wines.
Article
Pharmacology & Pharmacy
Sabrina Wohlfart, Michael Kilian, Philip Storck, Thomas Gutsmann, Klaus Brandenburg, Walter Mier
Summary: A novel method for precise quantification of Pep19-2.5 in biological samples has been developed in this study, which is crucial for the treatment of sepsis. The method utilizes mass spectrometry and labeled amino acid residues to reliably quantify the peptide content.
Article
Biochemistry & Molecular Biology
Heesoo Jeong, Yan Yu, Henrik J. Johansson, Frank C. Schroeder, Janne Lehtio, Nathaniel M. Vacanti
Summary: Stable-isotope tracing is a method used to measure intracellular metabolic pathway utilization by feeding a cell system a stable-isotope-labeled tracer nutrient. An algorithm and tool, PolyMID-Correct, have been developed to computationally remove the influence of naturally occurring heavy isotopes, making the method more accurate and reliable. This algorithm is applicable to data collected on both low- and high-mass resolution mass spectrometers, and PolyMID-Correct is open source under an MIT license.
Article
Chemistry, Analytical
Bernard Evers, Albert Gerding, Theo Boer, M. Rebecca Heiner-Fokkema, Mathilde Jalving, S. Aljoscha Wahl, Dirk-Jan Reijngoud, Barbara M. Bakker
Summary: C-13 isotope tracing combined with absolute metabolite concentration quantification enables detailed characterization of the metabolome. Our newly developed method allows simultaneous quantification of metabolite concentrations and C-13 isotope enrichments in a single C-13-labeled sample.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Max L. Feuerstein, Ruwan T. Kurulugama, Stephan Hann, Tim Causon
Summary: This work focused on implementing ion mobility and a prototype quadrupole driver in data independent acquisition for non-targeted metabolomics to improve confidence in identity confirmation workflows. By combining hardware performance and software tools, 87 metabolites were identified using new acquisition and data processing approaches.
ANALYTICA CHIMICA ACTA
(2021)
Article
Agriculture, Multidisciplinary
Mengyu Shen, Xiaofang Liu, Xiangxin Xu, Yinyin Wu, Jixian Zhang, Li Liang, Chaoting Wen, Xudong He, Xin Xu, Guoyan Liu
Summary: Isotope-labeled four polycyclic aromatic hydrocarbons were used to study the migration and distribution of PAH4 in oil and French fries during frying. The results showed that PAH4 mainly distributed in the crust of the French fries, especially five-ring PAHs. The migration of PAH4 was mainly caused by oil absorption of French fries, which was influenced by the fluidity and polar component of the oil. Higher frying temperature enhanced the crust ratio and porous structure of French fries.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sergey Osipenko, Anton Bashilov, Anna Vishnevskaya, Lidiia Rumiantseva, Anna Levashova, Anna Kovalenko, Boris Tupertsev, Albert Kireev, Eugene Nikolaev, Yury Kostyukevich
Summary: Mass spectrometry is a crucial technique for studying the metabolic pathways of living organisms. High-resolution mass spectrometry allows for untargeted metabolomics studies, even for multiple compounds labeled simultaneously. We demonstrated the capabilities of high-resolution mass spectrometry in studying the metabolism of a model plant, and showed the usefulness of in vivo labeling with heavy water and tandem mass spectrometry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Penghui Lin, Teresa W. M. Fan, Andrew N. Lane
Summary: NMR is a powerful tool for identifying and quantifying compounds in complex mixtures, without the need for individual standards or chromatographic separation. Stable Isotope Resolved Metabolomics (SIRM) is an approach that tracks the fate of individual atoms from precursors to metabolic transformation, creating atom-resolved metabolic fate maps. However, cell or tissue extracts result in complex NMR spectra, requiring additional tools to determine site-specific isotopomer distributions.
Article
Biochemical Research Methods
Xueying Wang, Chengting Luo, Lina Xu, Yusong Wang, Lv Jun Guo, Yupei Jiao, Haiteng Deng, Xiaohui Liu
Summary: Isotope tracing assisted metabolic analysis is a useful tool to understand metabolic regulation. This study presents a strategy called pseudo-targeted profiling of isotopic metabolomics (PtPIM) to expand the analysis of isotope labeled metabolites. The PtPIM method successfully broadened metabolite coverage in isotope tracing analysis and revealed the effects of rotenone on mitochondrial function.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Chemistry, Analytical
Xuan Lu, Xinli Zhu, Deying Chen, Jiahang Zhou, Jiong Yu, Jue Xie, Senxiang Yan, Hongcui Cao, Liang Li, Lanjuan Li
Summary: This study developed a workflow to investigate the metabolic changes in blood components after irradiation, identifying specific metabolites and pathways affected by irradiation. The results showed modulation of taurine and hypotaurine metabolism in plasma, as well as purine metabolism in RBCs and PBMCs. These findings offer insights into the impact of irradiation on blood metabolism.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Food Science & Technology
Yaqian Geng, Zijing Xu, Yiran Yu, Jinbo Yao, Wei Li, Fang Chen, Xiaosong Hu, Junfu Ji, Lingjun Ma
Summary: A novel stable isotope-labeling approach combined with high-resolution mass spectrometry was used to track quinone reaction pathways in wines and model systems. Unexpected binding products of quinone-quinone and quinone-catechol were discovered, which were not derived from nucleophilic or redox reactions. Self-coupling of semiquinone radicals and charge transfer reactions were proposed as the possible mechanisms for the formation of these products. These findings provide new insights into the metabolic pathways of quinones in foods.
FOOD RESEARCH INTERNATIONAL
(2023)
Article
Chemistry, Analytical
Xiaoling Su, Deying Chen, Liang Li, Lanjuan Li
Summary: The study demonstrates that perfusion can significantly alter the liver metabolome, recommending the use of non-perfused liver for comprehensive liver metabolomics analysis for high coverage.
ANALYTICA CHIMICA ACTA
(2021)
Article
Geochemistry & Geophysics
Elliott P. Mueller, Fenfang Wu, Alex L. Sessions
Summary: Natural-abundance stable isotope compositions are important tools for understanding complex processes. This article presents a new isotope modelling software tool called QIRN, which combines computational strategies used in metabolic modeling with natural isotope fractionations. QIRN treats isotopic properties as distributions of discrete isotopologues, enabling models of reaction networks with unprecedented complexity. QIRN can model any physical, chemical or biological process and has a diverse range of applications. It reproduces outputs from previous models and predicts isotopic anomalies measured in nature.
Article
Marine & Freshwater Biology
Eric Bollinger, Jochen P. Zubrod, Marco Konschak, Ralf Schulz, Mirco Bundschuh
Summary: Stable isotope analysis is an important technique in food web ecology, but its effectiveness can be unclear in complex systems. The use of heavy isotope tracers has been suggested as a way to enhance the utility of stable isotope analysis, but this study found that labeling could potentially affect isotopic fractionation and bias conclusions. While the physiological and activity levels of organisms in autotrophy-based and detritus-based aquatic food webs were not significantly affected by labeling, the study supported the isotopic redundancy hypothesis, which suggests that metabolic processes can be altered by discrete quantum mechanical states.
AQUATIC TOXICOLOGY
(2023)
Article
Chemistry, Analytical
Yasin El Abiead, Maximilian Milford, Harald Schoeny, Mate Rusz, Reza M. Salek, Gunda Koellensperger
Summary: When performing chromatography-mass spectrometry-based nontargeted metabolomics or exposomics, evaluating the completeness and accuracy of feature tables is crucial. The newly developed mzRAPP method allows the generation of benchmark peak lists using known molecules, facilitating the improvement of quantitative biological understanding.
ANALYTICAL CHEMISTRY
(2022)
Article
Chemistry, Analytical
Yasin El Abiead, Christoph Bueschl, Lisa Panzenboeck, Mingxun Wang, Maria Doppler, Bernhard Seidl, Juergen Zanghellini, Pieter C. Dorrestein, Gunda Koellensperger
Summary: This study utilized 13C labeled and unlabeled Pichia pastoris extracts to identify heterogeneous multimerization in biological samples and successfully annotated the monomeric partners of these heteromers. Additionally, they created the first MS/MS library that included data from heteromultimers and demonstrated the relevance of these newly annotated ions to other publicly available datasets. Furthermore, their workflow detected metabolite features originating from heterodimers in other datasets as well.
ANALYTICA CHIMICA ACTA
(2022)
Article
Biochemical Research Methods
Kevin Mildau, Justin J. J. van der Hooft, Mira Flasch, Benedikt Warth, Yasin El Abiead, Gunda Koellensperger, Jurgen Zanghellini, Christoph Bueschl
Summary: This article presents a method for targeted and untargeted detection of homologue series using an R package, homologueDiscoverer, and provides evaluation and management through interactive plots and simple local database functionalities.
Article
Geriatrics & Gerontology
Paola Sebastiani, Zeyuan Song, Dylan Ellis, Qu Tian, Michaela Schwaiger-Haber, Ethan Stancliffe, Michael S. Lustgarten, Cory C. Funk, Priyanka Baloni, Cong-Hui Yao, Shakchhi Joshi, Megan M. Marron, Anastasia Gurinovich, Mengze Li, Anastasia Leshchyk, Qingyan Xiang, Stacy L. Andersen, Mary F. Feitosa, Svetlana Ukraintseva, Mette Soerensen, Oliver Fiehn, Jose M. Ordovas, Marcia Haigis, Stefano Monti, Nir Barzilai, Sofiya Milman, Luigi Ferrucci, Noa Rappaport, Gary J. Patti, Thomas T. Perls
Summary: By conducting a meta-analysis of five studies, this research identified a signature of 19 metabolites significantly associated with the e2 allele of the APOE gene. These metabolites were primarily glycerolipids and glycerophospholipids, which were higher in carriers of the e2 allele. Additionally, one organic acid metabolite was also found to be associated with the e2 allele. However, no significant associations were found with metabolites in the e4 allele group.
Article
Biochemistry & Molecular Biology
Judy Baek, Kelli Sas, Chenchen He, Viji Nair, William Giblin, Ayaka Inoki, Hongyu Zhang, Yingbao Yang, Jeffrey Hodgin, Robert G. Nelson, Frank C. Brosius III, Matthias Kretzler, Paul M. Stemmer, David B. Lombard, Subramaniam Pennathur
Summary: Early DKD is characterized by metabolic reprogramming, and SIRT5 may play a role in regulating metabolism in DKD by removing acyl-coenzyme A-derived posttranslational modifications.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Plant Sciences
Mariavittoria Verrillo, Gunda Koellensperger, Marlene Puehringer, Vincenza Cozzolino, Riccardo Spaccini, Evelyn Rampler
Summary: In this study, humic substances and compost teas extracted from artichoke and coffee grounds were applied on Ocimum basilicum plants to enhance the yield of specific metabolites with nutraceutical and antibacterial features. The results showed that these substances improved the antioxidant and antimicrobial activity of basil metabolites and promoted the synthesis of aromatic amino acids and phenolic compounds.
Article
Biochemistry & Molecular Biology
Xiangfeng Niu, Ethan Stancliffe, Susan J. Gelman, Lingjue Wang, Michaela Schwaiger-Haber, Joe L. Rowles, Leah P. Shriver, Gary J. Patti
Summary: In this study, an approach to resolve the fluxes of NADPH in the cytosol and mitochondria was introduced using deuterium tracing. It was found that challenges in the cytosol affected NADPH fluxes in the cytosol, while challenges in the mitochondria affected NADPH fluxes in the mitochondria. This work highlights the value of using proline labeling as a reporter system for studying compartmentalized metabolism and reveals independent regulation of NADPH homeostasis in the cytosol and mitochondria, without evidence for NADPH shuttle activity.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Michaela Schwaiger-Haber, Ethan Stancliffe, Dhanalakshmi S. Anbukumar, Blake Sells, Jia Yi, Kevin Cho, Kayla Adkins-Travis, Milan G. Chheda, Leah P. Shriver, Gary J. Patti
Summary: Tumors are heterogeneous and consist of various cell types in different microenvironments. The integration of mass spectrometry imaging (MSI), stable isotope labeling, and isotopologue spectral analysis enables the mapping of metabolite distributions and metabolic fluxes in the brains of mice with GL261 glioma. This approach reveals alterations in anabolic pathways, specifically an increase in de novo fatty acid synthesis and elongation fluxes in the glioma compared to surrounding healthy tissue.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Felina Hildebrand, Harald Schoeny, Evelyn Rampler, Gunda Koellensperger
Summary: Lipidomics studies focus on identifying and quantifying lipids comprehensively. Reversed phase liquid chromatography (RP-LC) coupled with high resolution mass spectrometry (MS) is commonly used for lipid identification, but accurate lipid quantification remains challenging. We established a dual flow injection and chromatography setup to address the issue of solvent composition affecting ionization response. Our results confirmed that changing solvent conditions significantly influence ionization response and quantification biases. This finding was further supported by quantifying human plasma lipids and a panel of lipid species standards under different ionization conditions.
ANALYTICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Lukas Scheibelberger, Toda Stankovic, Marlene Puehringer, Hanspeter Kaehlig, Theresa Balber, Eva-Maria Patronas, Evelyn Rampler, Markus Mitterhauser, Arvand Haschemi, Katharina Pallitsch
Summary: Fluorinated carbohydrates are valuable tools for studying metabolic pathways, and this study explores their potential in investigating the metabolism of rare sugars in the pentose phosphate pathway (PPP). Two fluorinated derivatives of d-sedoheptulose were synthesized, with 4DFS showing potential as a new PPP imaging probe.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Environmental Sciences
Seonyoung Park, Amber L. Cathey, Wei Hao, Lixia Zeng, Subramaniam Pennathur, Max T. Aung, Zaira Rosario-Pabon, Carmen M. Velez-Vega, Jose F. Cordero, Akram Alshawabkeh, Deborah J. Watkins, John D. Meeker
Summary: The study found that gestational exposure to phthalates, a type of plasticizer, may lead to preeclampsia and preterm birth through pathways such as endocrine disruption, oxidative stress, and inflammation. The researchers investigated the associations between urinary phthalates and their mixtures with plasma eicosanoid levels during pregnancy. In both single-pollutant analysis and mixture analysis, associations with certain phthalate metabolites were found, indicating the complexity of the physiological impacts of phthalate exposure.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Environmental Sciences
S. V. Thangaraj, L. Zeng, S. Pennathur, R. Lea, K. D. Sinclair, M. Bellingham, N. P. Evans, R. Auchus, V. Padmanabhan
Summary: This study investigates the impact of exposure to environmental chemicals (ECs) derived from human waste on the maternal steroid, cytokine, and oxidative stress environments. The results show that exposure to biosolids disrupts these environments and may contribute to reproductive and metabolic disruptions in offspring. This research is important for understanding the effects of ECs on pregnant individuals and their babies.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Article
Medicine, Research & Experimental
Madathilparambil Suresh, Sinan Aktay, George Yalamanchili, Sumeet Solanki, Dily Thazhath Sathyarajan, Manikanta Swamy Arnipalli, Subramaniam Pennathur, Krishnan Raghavendran
Summary: Research findings indicate that hypoxia from lung injury following trauma is regulated by hypoxia-inducible factor 1 alpha (HIF-1 alpha), driving the acute inflammatory response in airway epithelial cells (AEC). Metabolomics profiling reveals increased glycolytic and TCA intermediates in Type II AEC after lung contusion, while succinate directly promotes inflammation in human small AEC.
Article
Biochemistry & Molecular Biology
Stephanie A. Eid, Phillipe D. O'Brien, Katharina H. Kretzler, Dae-Gyu Jang, Faye E. Mendelson, John M. Hayes, Andrew Carter, Hongyu Zhang, Subramaniam Pennathur, Frank C. C. Brosius III, Emily J. Koubek, Eva L. Feldman
Summary: Patients with type 2 diabetes often develop microvascular complications, including diabetic kidney disease and diabetic peripheral neuropathy. This study compared the effects of three dietary interventions on a type 2 diabetes mouse model and found that they improved weight and glycemic status and alleviated diabetic kidney disease, but did not impact diabetic peripheral neuropathy. Additionally, diets that decrease fat mass may be a promising non-pharmacological approach to improve diabetic peripheral neuropathy in type 2 diabetes.
Review
Physiology
Markus Bitzer, Wenjun Ju, Lalita Subramanian, Jonathan P. Troost, Joseph Tychewicz, Becky Steck, Roger C. Wiggins, Debbie S. Gipson, Crystal A. Gadegbeku, Frank C. Brosius III, Matthias Kretzler, Subramaniam Pennathur
Summary: The research on kidney diseases is changing due to the rapid growth and advancements in omics technologies. However, the analysis, integration, and interpretation of big data have been a challenge in using these technologies. To address this issue, the University of Michigan's MKTC has established the Applied Systems Biology Core to provide support and services for the global kidney research community.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)